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Hydrophobic core structure of macromomycin – the apoprotein of the antitumor antibiotic auromomycin – fuzzy oil drop model applied

Roterman-Konieczna I., Banach M., Konieczny L.

Bio-Algorithms and Med-Systems

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2015

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Vol. 11, no. 3

177--181

EN

The fuzzy oil drop model was applied to analyze the structure of macromomycin, the apoprotein of the antitumor antibiotic auromomycin, revealing the differentiation of β-structural fragments present in β-sandwich. The seven-stranded antiparallel β-barrel and two antiparallel β-sheet ribbons represent the highly ordered geometry of the structure. However, participation in hydrophobic core formation appears different. The structure of the complete domain represents the status of the irregular hydrophobic core; however, some β-structural fragments appear to represent the hydrophobicity density distribution accordant with the idealized distribution of hydrophobicity as expected using the fuzzy oil drop model. Four β-structural fragments generating one common layer appear to be unstable in respect to the general structure of the hydrophobic core. This area is expected to be more flexible than other parts of the molecule. The protein binds the ligand – chromophore, two 2-methyl-2,4-pentanediol – in a well- defined cleft. The presence of this cleft makes the general structure of the hydrophobic core irregular (as it may be interpreted using the fuzzy oil drop model). Two short loops generated by two SS bonds fit very well to the general distribution of hydrophobicity density as expected for the model. No information about the potential amyloidogenic character of this protein is given in the literature; however, the specificity of the hydrophobicity distribution profile is found to be highly similar to the one observed in transthyretin (Banach M, Konieczny L, Roterman I. The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function. J Theor Biol 2014;359:6–17), suggesting a possible tendency to turn to the amyloid form. A detailed analysis of macromomycin will be given, and a comparable analysis with other proteins of β-sandwich or β-barrel will be presented.

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Structural role of exons in hemoglobin

Piwowar M., Banach M., Konieczny L., Chomilier J., Roterman I.

Bio-Algorithms and Med-Systems

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2013

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Vol. 9, no. 2

81--90

EN

The role of exons can be studied on many levels, one of which pertains to protein structure. It is a well-known fact that secondary structural motifs do not directly correspond to exons: helices, β-sheets and loops have all been identified as encoded by more than one exon. The relation between exon fragments and their involvement in shaping the three-dimensional (3D) structure of a protein body is subject to ongoing studies. In particular, the role of exons in stabilizing tertiary structures can be related to the structure of the hydrophobic core of the protein. Participation of specific polypeptide fragments (single exons) in hydrophobic stabilization reveals the role played by each fragment. In the course of the presented research, exons in selected proteins have been identified on the basis of GenBank files, imported from the nucleotide database at the National Center of Biotechnology Information. Amino acid sequences representing each exon were subsequently traced to parts of 3D structural forms. The participation of each exon fragment in shaping the hydrophobic core of the protein was measured using divergence entropy calculations. It was found that each protein contains at least one exon which encodes a structural fragment in accordance with the theoretical hydrophobic core model. This implies that the likely role of at least one exon in each protein is to generate a hydrophobic core which is, in turn, responsible for tertiary structural stabilization.

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Structural role of exon-coded fragments in proteins

Piwowar M., Banach M., Konieczny L., Roterman I.

Bio-Algorithms and Med-Systems

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2013

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Vol. 9, no. 3

103--114

EN

This article describes the role of protein fragments encoded by individual exons. Structural analysis of the hydrophobic core on the basis of the “fuzzy oil drop” model – in whole molecules as well as in fragments encoded by specific exons – indicates that, in each protein, at least one exon encodes a fragment, which is consistent with the theoretical distribution of hydrophobicity density. Quantitative assessment of the properties of such exons in selected proteins enables the model to be applied in identifying the structural (stabilizing) role of polypeptide chains encoded by individual exons. This is viewed as a preliminary step toward future exploitation of this technique in studying the alternative splicing phenomenon.

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Measurement of hydrophobicity distribution in proteins – complete redundant Protein Data Bank

Sałapa K, Kalinowska B., Jadczyk T., Roterman I.

Bio-Algorithms and Med-Systems

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2012

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Vol. 8, no. 2

195--206

EN

The divergence entropy: O/T and O/R measuring the distance between observed/theoretical and observed/random distributions was applied to identify the category of protein structures in respect to the hydrophobic core in protein molecules. The naive interpretation was applied treating the proteins of O/T < O/R as the molecules of hydrophobic core accordant with the theoretically assumed. The proteins of O/T > O/R are treated as representing the hydrophobic core not accordant with the assumed one. The large scale computing was performed (PDB data set) to reveal whether other than simple inequality relation should be used for this identification. The cluster analysis was applied to identify the relation O/T versus O/R as the discrimination factor to classify the category of proteins in respect to their structural form of hydrophobic core.